Chinese Medical Journal最新文献

Background: The impact of intracranial atherosclerosis, assessed using precise methods, on cognitive function and dementia remains an area of ongoing research. This study aimed to explore the association of intracranial atherosclerosis with incident dementia in middle-aged community dwellers.

Methods: A total of 1009 subjects from the Shunyi study started from 2013, with a mean age of 55.3 ± 8.6 years, were included. With magnetic resonance angiography (MRA) and high-resolution magnetic resonance imaging (HRMRI), intracranial artery stenosis and plaque were assessed. Cognitive function was evaluated twice at baseline (2013-2016) and at follow-up (2019-2021). A logistic regression model was used to test the associations.

Results: The study cohort consisted of 371 males and 638 females, with a mean educational attainment of 6.7 ± 3.2 years. During a median 5.1-year follow-up, 29 incident cases of dementia were identified. Posterior circulation stenosis on MRA (odds ratio [ORs] 3.47, 95% confidence interval [CI] 1.19-10.15; P = 0.023) and basilar artery plaque on HRMRI (OR 5.51, 95% CI 1.79-16.96; P = 0.003) were associated with incident dementia, adjusting for confounding factors. While the middle cerebral artery plaque was a risk factor for cognitive decline.

Conclusions: Intracranial atherosclerosis, especially posterior circulation, was independent risk factor of incident dementia in middle-aged population, implying more studies for large artery atherosclerosis therapy in the prevention of midlife dementia.

Background: Severe white matter lesions (WMLs) have been linked to poorer functional outcomes following endovascular therapy (EVT) in patients with acute ischemic stroke (AIS) due to large-vessel occlusion (LVO). However, the absence of a control group in previous studies has limited the ability to determine the benefit of EVT to patients with severe WMLs.

Methods: This work is a secondary analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core trial, a multicenter, randomized controlled trial conducted at 46 comprehensive stroke centers across China, which enrolled 456 patients with AIS with anterior-circulation LVO and large ischemic cores between October 2020 and May 2022. WML severity was graded using the van Swieten Scale on pretreatment noncontrast computed tomography (CT). For supplementary analyses, WML severity was further assessed using T2 fluid-attenuated inversion recovery (T2-FLAIR) magnetic resonance imaging (MRI) and graded according to the Fazekas scale, with WMLs categorized into periventricular and deep subtypes. Treatment effect on the primary outcome (90-day modified Rankin Scale [mRS] score) was assessed using multivariable ordinal logistic regression, and a treatment-by-WML interaction term was tested to evaluate effect modification.

Results: In patients with absent-to-moderate WMLs, EVT was associated with a favorable shift in the distribution of 90-day mRS scores (adjusted common odds ratio [cOR] 2.15, 95% confidence interval [CI, 1.48-3.13], P <0.001). However, this benefit was less pronounced in those with severe WMLs (adjusted cOR 2.25, 95% CI [0.95-5.30], P = 0.065). No significant interaction between WML severity and treatment effect was detected (Pinteraction = 0.888). Similarly, only among patients with absent-to-moderate WMLs, EVT significantly increased rates of mRS scores of 0-2 (adjusted OR 4.86, 95% CI [2.66-8.86], P <0.001), the rates of mRS scores of 0-3 (adjusted OR 2.23, 95% CI [1.39-3.57], P = 0.001), and the rates of early neurological improvement (adjusted OR 5.22, 95% CI [1.31-20.79], P = 0.019) compared to medical management alone. Supplementary analyses using T2-FLAIR MRI to stratify patients by WML burden yielded results consistent with those of the primary analyses.

Conclusions: EVT significantly improved functional outcomes in patients with LVO-AIS with absent-to-moderate WMLs, while the benefit in those with severe WMLs appeared less pronounced. However, estimates within subgroups were underpowered. Future pooled analyses of randomized clinical trials with adequate statistical power are needed to clarify the impact of WML severity on EVT outcomes and to refine patient selection criteria.

Registration: ClinicalTrials.gov, No. NCT04551664.

Abstract: The gut-brain axis is a complex, bidirectional network of communication systems that integrates neural, endocrine, and immune pathways, as well as metabolic processes, to regulate homeostasis and maintain physiological and cognitive equilibrium. Central to this axis is the gut microbiota, which exerts a profound influence on brain function through microbial metabolites, including short-chain fatty acids, tryptophan metabolites, and bile acids. Disruption of this microbial balance, known as dysbiosis, has been implicated in the onset and progression of major neuropsychiatric and neurodegenerative disorders, including depression, Alzheimer's disease, and Parkinson's disease. This review critically examines the mechanistic underpinnings of the gut-brain axis, emphasizing metabolic, immunological, and neuroendocrine signaling as key mediators. Furthermore, it explores how dietary components, particularly fiber, polyphenols, and fermented foods, modulate gut microbial composition and function to influence brain health. Emerging therapeutic strategies, such as probiotics, prebiotics, and fecal microbiota transplantation, are discussed, along with the potential of personalized targeted intervention. By integrating current findings, this review underscores the gut-brain axis as a dynamic interface that not only influences neurological and psychiatric outcomes but also represents a promising target for therapeutic intervention.

Abstract: Pancreatic ductal adenocarcinoma (PDAC), the deadliest epithelial malignancy, is increasingly prevalent and contributes significantly to cancer-related mortality. Research over the past decade has demonstrated that microbiota may play a pivotal role in both PDAC oncogenesis and its resistance to chemotherapy. Emerging preclinical and clinical data highlight the impact of microbiota on therapeutic outcomes in PDAC patients. This review systematically explores the role and underlying mechanisms of microbiota in PDAC, with a particular focus on their clinical implications and translational potential in disease progression and therapeutic responses. Finally, this review addresses the potential of microbiome-based therapies to enhance the efficacy of PDAC treatments.

Background: Intron retention (IR) is an important biological process associated with disease development. However, the role of IR in the progression of tuberculosis (TB) remains unexplored. Therefore, this study aimed to characterize the dynamic IR landscape during TB progression and elucidate the role of DNASE1L2-IR in this process.

Methods: We conducted a comprehensive high-throughput sequencing analysis using 1729 samples from 19 public datasets and identified candidate IR events associated with TB progression. We then validated these candidate IR events in three macrophage infection models by quantitative polymerase chain reaction and revealed the underlying molecular mechanisms by investigating the subcellular localization and functional roles of their associated isoforms.

Results: In an analysis of 1729 clinical specimens, we found genome-wide intron-splicing reprogramming in host cells during TB progression. Notably, deoxyribonuclease 1 like 2 (DNASE1L2, a gene encoding deoxyribonuclease)-IR exhibited striking differences among healthy controls, individuals with latent TB infection, and individuals with active TB (Padj <0.05), particularly between progressors and nonprogressors (Padj <0.0001). Similar differences were observed in Mycobacterium tuberculosis (M. tuberculosis) infection models in vitro; as the stimulation increased in concentration or duration, IR initially increased but subsequently decreased. DNASE1L2-IR generated two transcript isoforms: a long isoform (DNASE1L2-L) and a short isoform (DNASE1L2-S). Upon stimulation, DNASE1L2-L appeared in the cytoplasm, whereas DNASE1L2-S remained membrane-anchored. Deoxyribonuclease activity assays revealed that compared with DNASE1L2-S, DNASE1L2-L exhibited significantly greater enzymatic activity against plasmid and M. tuberculosis DNA substrates and more effectively suppressed the release of interleukin-1beta and tumor necrosis factor alpha, indicating isoform-specific functional divergence in inflammatory regulation.

Conclusion: These findings identify DNASE1L2-IR splicing dynamics as a novel biomarker for monitoring TB progression and reveal a host-defense mechanism in which DNASE1L2-IR regulates M. tuberculosis DNA degradation to modulate TB progression.